5-HT1 receptors mediating contraction in bovine cerebral arteries: a model for human cerebrovascular '5-HT1D beta' receptors

Eur J Pharmacol. 1993 Sep 21;242(1):75-82. doi: 10.1016/0014-2999(93)90012-7.

Abstract

We report on the pharmacological profile of the 5-HT receptor which induces contraction of the bovine isolated cerebral arteries. Several 5-HT receptor agonists were tested for their ability to induce vasoconstriction in bovine pial arteries and their potencies were compared to that of 5-HT. The rank order of agonist potency can be summarized as 5-carboxamidotryptamine (5-CT) = RU 24969 > or = 5-HT > sumatriptan > alpha-methyl-5-HT > methysergide > 2-methyl-5-HT > ((+-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene (8-OH-DPAT). Only methysergide induced a contraction which was smaller than that elicited by 5-HT. Antagonists with selective affinity at 5-HT1A/1B (propranolol), 5-HT1C (mesulergine), 5-HT2 (ketanserin, mianserin) and 5-HT3 (MDL 72222) sites were inactive to block the 5-HT-induced contraction. In contrast, the 5-HT1/5-HT2 receptor antagonists methiothepin and metergoline inhibited the 5-HT-induced response with relatively high affinity (pA2 = 8.16 +/- 0.26 and 6.73 +/- 0.05, respectively). Overall, this pharmacological profile indicated clearly that a 5-HT1 receptor, most closely related to the 5-HT1D subtype, is responsible for the 5-HT-induced contraction of bovine cerebral arteries. Correlation analysis of the potencies of a series of 5-HT receptor agonists and antagonists in bovine and human cerebrovascular preparations showed a highly significant positive correlation (r = 0.94, P = 0.0051).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cerebral Arteries / drug effects
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Models, Cardiovascular
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Receptors, Serotonin / drug effects*
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*

Substances

  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin